molecules Review Is the Antidepressant Activity of Selective Serotonin Reuptake Inhibitors Mediated by Nicotinic Acetylcholine Receptors? Hugo R. Arias 1,*,†, Katarzyna M. Targowska-Duda 2,†, Jesús García-Colunga 3,† and Marcelo O. Ortells 4 1 Department of Pharmacology and Physiology, Oklahoma State University College of Osteopathic Medicine, Tahlequah, OK 74464, USA 2 Department of Biopharmacy, Medical University of Lublin, 20-093 Lublin, Poland;
[email protected] 3 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro 76230, Mexico;
[email protected] 4 Facultad de Medicina, Universidad de Morón, CONICET, Morón 1708, Argentina;
[email protected] * Correspondence:
[email protected]; Tel.: +1-918-525-6324; Fax: +1-918-280-2515 † These authors contributed equally to this work. Abstract: It is generally assumed that selective serotonin reuptake inhibitors (SSRIs) induce an- tidepressant activity by inhibiting serotonin (5-HT) reuptake transporters, thus elevating synaptic 5-HT levels and, finally, ameliorates depression symptoms. New evidence indicates that SSRIs may also modulate other neurotransmitter systems by inhibiting neuronal nicotinic acetylcholine receptors (nAChRs), which are recognized as important in mood regulation. There is a clear and strong association between major depression and smoking, where depressed patients smoke twice as much as the normal population. However, SSRIs are not efficient for smoking cessation therapy. In patients with major depressive disorder, there is a lower availability of functional nAChRs, although Citation: Arias, H.R.; their amount is not altered, which is possibly caused by higher endogenous ACh levels, which Targowska-Duda, K.M.; consequently induce nAChR desensitization. Other neurotransmitter systems have also emerged García-Colunga, J.; Ortells, M.O.